Arterial chemoreceptors play an important role in the cardiovascular responses to severe hypoxemia and hypercapnia. Major objectives of the proposed research are a better understanding of mechanisms of activation of chemoreceptors and of the responses which the chemoreceptors initiate. Carotid chemoreceptors and of the responses which the chemoreceptors initiate. Carotid chemoreceptors of dogs will be stimulated by injecting drugs into the common carotid artery or by perfusing the common carotid artery with hypoxic hypercapnic blood. Ventilatory responses will be observed by measuring changes in tidal volume, ventilatory rate, and expired CO2. Cardiovascular responses will be determined by measuring heart rate and systemic arterial pressure, and by observing vascular responses in perfused gracilis muscle and left circumflex coronary artery. Responses to injections into the carotid chemoreceptor of vasodilator drugs, bradykinin and nitroglycerin, will be observed. Responses to intracarotid dopamine (a catecholamine which may have an important role in the physiologic function of chemoreceptors) will be measured in dogs and responses to intravenous dopamine will be observed in normal men. An interaction of chemoreceptor and baroreceptor reflex effects on ventilation will be sought by stimulating chemoreceptors with nicotine at several levels of arterial pressure. Influences of chemoreceptor stimulation on distribution of blood flow, and modulation of the chemoreceptor reflex by the baroreceptor reflex, will be considered by examining the response of coronary, renal, mesenteric, and iliac vessels to physiologic stimulation of chemoreceptors at several levels of arterial pressure.